Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan.

AIM: To evaluate the effects of OGG1 (Ser326Cys, 11657A/G, and Arg154His) and APE1 (Asp148Glu, and T-656G) polymorphisms on colorectal cancer (CRC) risk. METHODS: We enrolled 727 cases newly diagnosed with colorectal adenocarcinoma and 736 age- and sex-matched healthy controls from a medical center in Taiwan. Genomic DNA isolated from the buffy coat was used for genotyping through polymerase chain reaction. Unconditional logistic regressions were used for calculating ORs and 95%CIs to determine the association between the genetic polymorphisms and CRC risk. Haplotype frequencies were estimated using PHASE software. Moreover, stratification analyses on the basis of sex, age at diagnosis, and tumor subsite and stage were performed. RESULTS: The CRC risk was higher in patients with the OGG1 326Ser/Cys + Cys/Cys genotype (OR = 1.38, 95%CI: 1.03-1.85, P = 0.030), particularly high in patients with stage III + IV cancer (OR = 1.48, 95%CI: 1.03-2.13) compared with patients with the Ser/Ser genotype. In addition, OGG1 11657G allele carriers had a 41% reduced CRC risk among stage 0-II patients (OR = 0.59, 95%CI: 0.35-0.98). The CRC risk was significantly higher among females with the APE1 Glu allele (OR = 1.41, 95%CI: 1.02-1.96). The APE1 148Glu/-656G haplotype was also associated with a significant CRC risk in females (OR = 1.36, 95%CI: 1.03-1.78). CONCLUSION: OGG1 and APE1 polymorphisms are associated with stage- and sex-specific risk of CRC in the Taiwanese population.

Polymorphisms of cytochrome P450 1A2 and N-acetyltransferase genes, meat consumption, and risk of colorectal cancer.

PURPOSE: Polymorphic cytochrome P-450 1A2, N-acetyltransferase 1, and 2 are important enzymes involved in the biotransformation of aromatic and heterocyclic amines known as carcinogens for colorectal cancer. A hospital-based study was designed to investigate the association between colorectal cancer and cytochrome P-450 1A2, N-acetyltransferase 1, and N-acetyltransferase 2, with the interaction of meat consumption. METHODS: We genotyped these polymorphisms for 727 colorectal cancer cases and 736 healthy controls. Information on sociodemographic characteristics and diet were ascertained using a structured questionnaire. RESULTS: The colorectal cancer risk was significantly increased in rapid N-acetyltransferase 1 carriers with high white meat consumption (almost every day) compared to those carrying the slow N-acetyltransferase 1 genotype with low white meat consumption (less than once a week, odds ratio, 3.00; 95 percent confidence interval, 1.83-4.92). Furthermore, a gene-gene interaction between cytochrome P-450 1A2*1C and N-acetyltransferase 1 was found and modulated by white meat consumption. CONCLUSIONS: N-acetyltransferase 1 might compete with cytochrome P-450 1A2*1C to increase the colorectal cancer risk in intermediate white meat consumers, whereas the rapid N-acetyltransferase 1 genotype may exert a harmful effect on individuals with high carcinogen exposure.

Association between polymorphisms of biotransformation and DNA-repair genes and risk of colorectal cancer in Taiwan.

The relationship between diet and colorectal cancer has been previously demonstrated and supported with strong epidemiological evidence. The role of genetic polymorphisms has, however, been less well elaborated upon. We conducted a hospital-based case-control study including 727 cases and 736 healthy controls to evaluate the associations of the polymorphic phase-I and -II biotransformations (CYP1A1, CYP1A2, GSTM1, GSTT1, GSTP1, NAT1 and NAT2) and DNA-repair enzymes (XRCC1, XRCC3 and XPD) with the risk of contracting colorectal cancer. We found that men featuring the CYP1A1*2C G/G genotype, the GSTT1 null genotype and XPD 751 with the Gln allele were associated with an elevated risk of colorectal cancer than were men who did not exhibit such genetic features. Multivariate logistic regression analysis revealed that individuals featuring more than two high-risk genotypes increased the colorectal-cancer risk 3.1-fold (OR = 3.1, 95% CI = 1.8-5.2). For women, subjects featuring the CYP1A1*2C G/G genotype and the XRCC3 Thr/Thr genotype faced a 3.1-fold greater risk (95% CI = 1.3-7.0) of colorectal cancer when compared to those featuring the CYP1A1*2C A allele and the XRCC3 Met allele. Taken together, this study suggests that polymorphisms of genes involved in biotransformation and DNA repair could modulate colorectal-cancer risk in Taiwan.

MS-920: DNA repair gene polymorphisms, diet and colorectal cancer risk in Taiwan.

This hospital-based case-control study examined whether polymorphic DNA repair genes: XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, play a role in the susceptibility to colorectal cancer. We genotyped these polymorphisms for 727 newly diagnosed colorectal adenocarcinoma cases and 736 age and sex matched healthy controls in Taiwan. Although the colorectal cancer risk was not significantly associated with these genes, the risk was significantly elevated in younger subjects (< or =60 years) with the XRCC1 399Arg/Arg genotype compared to those with XRCC1 399Gln allele (OR=1.46, 95% CI=1.06-2.99, P=0.02). The stratified analysis showed that XRCC3 interacted with meat consumption (P for interaction=0.02), but was limited to the low meat consumption (OR=2.34, 95% CI=1.28-4.29). Our results suggest that the XRCC1 Arg399Gln polymorphism may contribute to the risk of early-onset colorectal cancer and the XRCC3 Thr241Met polymorphism may modify the risk for meat-associated colorectal cancer.

Vegetable/fruit, smoking, glutathione S-transferase polymorphisms and risk for colorectal cancer in Taiwan.

AIM: To investigate the colorectal cancer risk associated with polymorphic GSTM1, GSTT1 and GSTP1 and the effect of diet and smoking. METHODS: With consents, genotypes of the genes were determined using PCR methods for 727 cases and 736 sex and age-matched healthy controls recruited at a medical center in the Northern Taiwan. Nurses who were blind to the study hypothesis conducted interviews with study participants for the information of socio-demographic variables, diet and smoking. RESULTS: There was no significant association between GSTM1 genotypes and the disease. Men, not women, with GSTT1 null genotype were at significant risk of colorectal cancer, but limited to rectal tumor, and in men aged 60 years and less. The corresponding association with the GSTP1 with G allele compared to GSTP1 A/A genotype was at borderline significance. Compared to men with GSTT1 present and GSTP1 A/A combined, men with both GSTT1 null and GSTP1 with G allele genotypes were at significant risk (odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.21-3.02), also limited to the rectal tumor and younger men. The beneficial effects of vegetable/fruit intake on colorectal cancer were much higher for men with GSTT1 present (OR = 0.32, 95%CI = 0.20-0.50) or GSTP1 A/A genotypes (OR = 0.40, 95%CI = 0.25-0.64). These effects remained significant for women. But, the greatest protective effect from vegetable/fruit intake for women was observed in those with GSTT1 null or GSTP1 with G allele genotypes. In addition, non-smoking men benefitted significantly from combined effect of higher vegetable/fruit intake and GSTT1 present or GSTP1 A/A genotypes with OR = 0.17 and 0.21 respectively. CONCLUSION: This study suggests that the GSTT1 gene can modulate the colorectal cancer risk and vegetable/fruit-related colorectal cancer risk, particularly in men of no smoking history.

Polymorphisms of the XRCC1, XRCC3, & XPD genes, and colorectal cancer risk: a case-control study in Taiwan.

BACKGROUND: Recent studies relating to the association between DNA repair-gene polymorphisms and colorectal cancer risk would, to the best of our knowledge, appear to be very limited. This study was designed to examine the polymorphisms associated with three DNA repair genes, namely: XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, and investigate their role as susceptibility markers for colorectal cancer. METHODS: We conducted a case-control study including 727 cases of cancer and 736 hospital-based age- and sex-matched healthy controls to examine the role of genetic polymorphisms of three DNA-repair genes (XRCC1, XRCC3 and XPD) in the context of colorectal cancer risk for the Taiwanese population. Genomic DNA isolated from 10 ml whole blood was used to genotype XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: The risk for colorectal cancer did not appear to differ significantly amongst individuals featuring the XRCC1 399Arg/Arg genotype (OR = 1.18; 95% CI, 0.96-1.45), the XRCC3 241Thr/Thr genotype (OR = 1.25; 95% CI, 0.88-1.79) or the XPD 751Gln allele (OR = 1.20; 95% CI, 0.90-1.61), although individuals featuring a greater number of risk genotypes (genotype with OR greater than 1) did experience a higher risk for colorectal cancer when compared to those who didn't feature any risk genotypes (Trend test P = 0.03). Compared with those individuals who didn't express any putative risk genotypes, individuals featuring all of the putative risk genotypes did experience a significantly greater cancer risk (OR = 2.43, 95% CI = 1.21-4.90), particularly for individuals suffering tumors located in the rectum (OR = 3.18, 95% CI = 1.29-7.82) and diagnosed prior to the age of 60 years (OR = 4.90, 95% CI = 1.72-14.0). CONCLUSIONS: Our results suggest that DNA-repair pathways may simultaneously modulate the risk of colorectal cancer for the Taiwanese population, and, particularly for rectal cancer and younger patients.

Risk factors for colorectal cancer in Taiwan: a hospital-based case-control study.

BACKGROUND AND PURPOSE: There have been few studies of the risk factors associated with colorectal cancer in Taiwan, a country of low incidence of the disease. This study investigated whether dietary and lifestyle factors correlate with colorectal cancer risks in Taiwan. METHODS: A total of 352 patients with colon cancer and 375 patients with rectal cancer histologically confirmed between 1995 to 1999 at a medical center in northern Taiwan were included in the study. They were age- and gender-matched with 736 healthy controls who were recruited from the health examination clinic at the same hospital. Dietary intake and lifestyle variables were ascertained using a standardized questionnaire. Unconditional multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The risk of colon cancer and of rectal cancer was inversely associated with vegetable/fruit consumption in both men and women. The adjusted ORs based on the highest versus the lowest tertile consumption were 0.36 (95% CI, 0.21 to 0.61) and 0.44 (95% CI, 0.27 to 0.72) for men, respectively. The corresponding ORs for women were 0.32 (95% CI, 0.19 to 0.56) and 0.39 (95% CI, 0.23 to 0.69), respectively. However, the highest versus the lowest tertile meat consumption was associated with significantly elevated risk in both men and women for both colon cancer (ORs, 1.85 and 2.29, respectively) and rectal cancer (ORs, 2.32 and 2.42, respectively). Risk also increased with less exercise, low or moderate coffee consumption, cigarette smoking and alcohol intake, and decreased with the frequency of fish/shrimp consumption among men. CONCLUSIONS: Consistent with the findings of previous studies in Western populations, this study found that vegetable and fruit consumption, less meat consumption, and exercise were associated with a reduced incidence of colorectal cancer in Taiwanese.